Iap2 is required for a sustained response in the Drosophila Imd pathway.

Fruit flies have effective immune response against Gram-negative bacteria. Upon infection, early JNK-signaling pathway mediated response is followed by the action of the Immune deficiency (Imd) signaling cascade, a Drosophila equivalent of mammalian TNF-receptor pathway, leading to the release of antimicrobial peptides. Recently, Tak1-binding protein 2 (Tab2) and Inhibitor of apoptosis 2 (Iap2) were identified as components of the Imd pathway. In this study, we carried out a genome-wide kinetic analysis of the role of Tab2 and Iap2 for immune response in Drosophila S2 cells using oligonucleotide microarrays. Tab2 RNAi abolished the induction of all immune response genes in S2 cells indicating its requirement for signaling both via the Imd and the JNK pathway. The role of Iap2 was more specific. Kinetic analysis indicated that Iap2 is required to sustain antimicrobial peptide gene expression in S2 cells. Furthermore, inactivation of Iap2 by RNAi resulted in impaired microbial resistance in Drosophila in vivo.